Journal of neural transmission
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Besides generally accepted lower analgesic potencies of opioids in neuropathic pain, our recent pharmacological reports have demonstrated that the effectiveness of the micro-opioid receptor (MOR) agonists in neuropathy might depends upon the chemical/structural property of these compounds (alkaloid vs. peptides). Such findings prompted us to investigate the changes in MOR mRNA expression (estimated by PCR) as well as MOR functional activity (examined by [(35)S]GTPgammaS binding) in the dorsal horn of the spinal cord and the dorsal root ganglia (DRG) of neuropathic rats at different time points after sciatic nerve ligation. We found that the spinal MOR mRNA level and agonist-stimulated [(35)S]GTPgammaS binding were not affected by nerve injury. ⋯ Thus, neuropathy-induced specific dysfunction of MOR to activate G-protein together with changes in the MOR synthesis might be related, at least in part, to diminish analgesic efficacy of morphine in neuropathic pain. Interesting observations from current studies are linked to endomorphins (EMs), which do not affect the G protein stimulation of MOR after nerve ligation. This intriguing property of EMs, together with previously reported high analgesic efficacy of these compounds indicate that chemically/structurally different MOR agonists, particularly morphine versus EMs, may differentially interact with receptors causing distinct pharmacological effects in chronic pain.